Best transplant outcomes
achieved when children receive kidneys from adults

Placing a kidney from an
adult donor into an infant or young child not only improves
recovery prospects, it produces the best survival rates of any
transplanted organ in any age group, according to a study by
Stanford medical researchers.

Oscar Salvatierra, MD,
professor of surgery and nephrology and director of kidney
transplantation at Lucile Packard Children's Hospital, said that
until now the gold standard has been transplantation between 19- to
45-year-old siblings with identical immune systems.

However, Salvatierra and
his collaborators demonstrated in their study that adult-sized
kidneys transplanted into infants and young children do better than
this standard, particularly after the first year. The study was
published in the Dec. 27 issue of Transplantation.

The
best results came with kidneys from living donors, particularly
when the donor was one of the child's parents. Adult cadaver
kidneys were less optimal but even they succeeded at least as well
over the long term as living-donor transplants to adult
recipients.

These findings appeared not
only in patients treated at Packard, but also in data from the
Scientific Renal Transplant Registry maintained by the United
Network for Organ Sharing, or UNOS, which includes all transplant
procedures performed in the United States.

"As
long as the adult kidney functions immediately in the child, there
is no kidney loss from irreversible acute rejection after the first
year," Salvatierra said. "The challenge then becomes keeping the
kidney functioning through the first year. Once the patient gets
past that milestone, then the kidney is going to do very
well."

Adequate blood flow is key.
The child's smaller heart, blood volume and vessels are
insufficient to satisfy the blood-flow demand of an adult-sized
kidney, posing the risk of malfunction if blood clots develop in
the kidney.

In
previous research, Salvatierra and his colleagues determined how
much blood flow is needed to support a transplanted adult kidney in
a child and developed a way of supplying it. By placing the child
on intravenous and gastric-tube fluids, venous pressure is raised
during surgery. Blood volume is then increased for at least six
months following the transplant. With this method, every
adult-to-child kidney transplant patient at Packard has survived
the first year.

Minnie M. Sarwal, MD, PhD,
a molecular biologist and assistant professor of pediatric
nephrology, collaborated with Salvatierra on the study. She has
considered why the larger, adult-size kidney would do better in
children than organs from donors the children's size.

"The
larger kidney confers some kind of immunological privilege. In
animal research, transplanting just one kidney between rats without
identical immune systems results in rejection unless drugs that
suppress the immune response are given. But transplanting two
kidneys is successful, even without drugs. Apparently, the larger
mass of donor tissue 'exhausts' the recipient's immune system and
allows it to tolerate the transplant."

Sarwal is now pursuing
experiments to identify this mechanism and use it.

"It
is likely that we can reduce the level of immunosuppressive drugs
in children receiving adult kidneys after the first year," she
said. "My goal is to find a test that tells precisely how much we
can reduce immunosuppression and still protect the transplanted
kidney from rejection over the long term. That will greatly improve
care for these children."

Other co-authors of the
study, which was funded by grants from the David and Lucile Packard
Foundation and UNOS, include Maria T. Millan, MD, an assistant
professor of surgery at Stanford, and J. Michael Cecka, PhD, of the
UCLA Tissue Typing Laboratory.